Repair Of Large Osteochondral Defects Research Articles

In vivo evaluation of additively manufactured multi-layered scaffold for the repair of large osteochondral defects

The repair of osteochondral defects is one of the major clinical challenges in orthopaedics. Well-established osteochondral tissue engineering methods have shown promising results for the early treatment of small defects. However, less success has been achieved for the regeneration of large defects, which is mainly due to the mechanical environment of the joint and the heterogeneous nature of the tissue. In this study, we developed a multi-layered osteochondral scaffold to match the heterogeneous nature of osteochondral tissue by harnessing additive manufacturing technologies and combining the established art laser sintering and material extrusion techniques. The developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen “sandwich” composite system. The microstructure and mechanical properties of the scaffold were examined, and its safety and efficacy in the repair of large osteochondral defects were tested in an ovine condyle model. The 12-week in vivo evaluation period revealed extensive and significantly higher bone in-growth in the multi-layered scaffold compared with the collagen–HAp scaffold, and the achieved stable mechanical fixation provided strong support to the healing of the overlying cartilage, as demonstrated by hyaline-like cartilage formation. The histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control group. Chondrogenic genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control group. The findings showed the safety and efficacy of the cell-free “translation-ready” osteochondral scaffold, which has the potential to be used in a one-step surgical procedure for the treatment of large osteochondral defects.Graphic abstract

Sheep condyle model evaluation of bone marrow cell concentrate combined with a scaffold for repair of large osteochondral defects.

AimsMinimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone.MethodsThe ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety.ResultsThe results six months postoperatively showed that there were no significant differences in bone regrowth and mineral density between BMC-treated animals and controls. A significant upregulation of messenger RNA (mRNA) for types I and II collagens in the BMC group was observed, but there were no differences in the formation of hyaline-like cartilage between the groups. A trend towards reduced sulphated glycosaminoglycans (sGAG) breakdown was detected in the BMC group but this was not statistically significant. Functional weightbearing was not affected by the inclusion of BMC.ConclusionOur results indicated that the addition of BMC to scaffold is safe and has some potentially beneficial effects on osteochondral-tissue regeneration, but not on the functional endpoint of orthopaedic interest.Cite this article: Bone Joint Res 2021;10(10):677–689.

CaAlg hydrogel containing bone morphogenetic protein 4-enhanced adipose-derived stem cells combined with osteochondral mosaicplasty facilitated the repair of large osteochondral defects.

Cartilage repair presents a challenge to clinicians and researchers. A more effective procedure that can produce hyaline-like cartilage is needed for articular cartilage repair. Mosaic osteochondral grafts for large osteochondral defects often show poor integration between the grafts and the surrounding normal cartilage, leading to defective cracks filled with fibrous tissue instead of hyaline-like cartilage. In the present study, we aimed to repair the defective cracks with a calcium alginate (CaAlg) hydrogel containing bone morphogenetic protein 4 (BMP4)-enhanced adipose-derived stem cells (ADSCs). ADSCs were transduced with BMP4 (B-ADSCs). The expression of BMP4 and type II collagen was confirmed using an enzyme-linked immunosorbent assay (ELISA). Swine models of large cartilage defects of the knee were constructed and received one of the four treatments: mosaicplasty only, mosaicplasty with the CaAlg hydrogel, mosaicplasty with the CaAlg hydrogel containing ADSCs, or mosaicplasty with the CaAlg hydrogel containing B-ADSCs injected into the defective cracks. Outcomes were evaluated at 12 and 24weeks after surgery. The in vitro study showed that the osteogenic and chondrogenic activities of the B-ADSCs were enhanced compared with those of the control. In vivo, in the group that received mosaicplasty-containing B-ADSCs, osteochondral tissue was completely integrated with an intact surface. Additionally, the histological scores of the mosaicplasty-containing B-ADSCs group were significantly higher than those of the other groups. Biomechanical examination confirmed that the neocartilage possessed properties similar to those of normal cartilage. Mosaicplasty and hydrogel containing B-ADSCs promoted the repair of large cartilage defects by regenerating hyaline cartilage and repairing dead spaces between osteochondral grafts and donor-site defects, thus improving the feasibility and success rate of one-stage complete repair surgery for large osteochondral defects. This proposed method provides a novel and effective means for the repair of large articular osteochondral defects.

Early tissue formation on whole‐area osteochondral defect of rabbit patella by covering with fibroin sponge

Large osteochondral defects have been difficult to repair via tissue engineering treatments due to the lack of a sufficient number of source cells for repairing the defect and to the severe mechanical stresses affecting the replacement tissue. In the present study, whole-area osteochondral defects of rabbit patella were covered and wrapped with a fibroin sponge containing chondrocytes, with or without Green Fluorescent Protein (GFP) transgenic marking, on the surface facing the osteochondral defect. Five of eight osteochondral defects that were covered with the chondrocyte-seeded fibroin sponges showed hyaline cartilage-like repair containing no fibroin fragments at 6 weeks after surgery. The repaired tissue showed a layer formation, which showed intensive safranin-O and toluidine blue staining, and which showed positive type II collagen immunostaining. The average surface coverage of the repaired cartilage was 53%. On average, 48% of the cells in the repaired tissue were derived from GFP transgenic chondrocytes, which had been seeded in the fibroin sponge. The fibroin-sponge covering had the potential to allow the early repair of large osteochondral defects. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1474-1482, 2016.

Repair of large osteochondral defects in a beagle model with a novel type I collagen/glycosaminoglycan-porous titanium biphasic scaffold

The limited repair potential of articular cartilage, which hardly heals after injury or debilitating osteoarthritis, is a clinical challenge. The aim of this work was to develop a novel type I collagen (Col)/glycosaminoglycan (GAGs)-porous titanium biphasic scaffold (CGT) and verify its ability to repair osteochondral defects in an animal model with bone marrow stem cells (bMSCs) in the chondral phase. The biphasic scaffold was composed of Col/GAGs as chondral phasic and porous titanium as subchondral phasic. Twenty-four full-thickness defects through the articular cartilage and into the subchondral bone were prepared by drilling into the surface of the femoral patellar groove. Animals were assigned to one of the three groups: 1) CGT with bMSCs (CGTM), 2) only CGT, and 3) no implantation (control). The defect areas were examined grossly, histologically and by micro-CT. The most satisfied cartilage repairing result was in the CGTM group, while CGT alone was better than the control group. Abundant subchondral bone formation was observed in the CGTM and CGT groups but not the control group. Our findings demonstrate that a composite based on a novel biphasic scaffold combined with bMSCs shows a high potential to repair large osteochondral defects in a canine model.

Repair of Large Osteochondral Defects With Mix-Mosaicplasty in a Goat Model

Osteochondral defects in weight-bearing regions must be repaired with cartilage and subchondral bone support simultaneously, as well as the integration between the 2, particularly in young, active patients. In this study, a new method called mix-mosaicplasty was used to reconstruct large osteochondral defects (6-mm diameter) in the weight-bearing region of the femoral condyle of goats. Two periosteum-bone plugs and 1 osteochondral plug harvested from the proximal tibia and intertrochlea groove were assembled to fill the defects in a mosaic mode. The goats were euthanized 16 weeks postoperatively, and the result of the repair process was assessed using macroscopy, morphologic analysis, electron microscope observation, glycosaminoglycan assay, and magnetic resonance imaging. Sixteen weeks postoperatively, the superficial surface of the defective region was covered with regenerated cartilage, and the periosteum-bone plugs were combined with each other. However, cleavage between cartilage plugs was noted. The donor site, which was filled with periosteum-bone plugs, was regenerated with fibrocartilage-like tissue. The repaired tissue was composed of small chondrocyte-like cells arranged tightly within an evenly distributed extracellular matrix containing type II collagen. Cells of the regenerated tissue in periosteum-bone plugs were smaller and distributed more densely. Electron microscopy demonstrated regular matrix fibers and abundant organelles within the repaired tissue. No significant differences of glycosaminoglycan content were observed between reconstructed tissue and normal hyaline cartilage. Magnetic resonance imaging revealed the healing process between plugs other than the control group. The new technique of mix-mosaicplasty can reconstruct full-thickness osteochondral compound defects in the weight-bearing region of the femoral condyle.

NEL-like molecule-1-modified bone marrow mesenchymal stem cells/poly lactic-co-glycolic acid composite improves repair of large osteochondral defects in mandibular condyle

Articular cartilage of the mandibular condyle has limited ability to regenerate itself after injury. This study was to investigate whether osteochondral defects in mandibular condyle could be repaired by NELL-1(NEL-like molecule-1)-modified autogenous bone marrow mesenchymal stem cells (BMMSCs) and poly lactic-co-glycolic acid (PLGA) composite. Osteochondral defects of 3mm-diameter × 5mm-depth were created unilaterally in the central part of the condyle in 50 adult goats. The injury sites were treated with NELL-1-modified BMMSCs/PLGA, BMMSCs/PLGA, PLGA alone, or left empty. The defect area was monitored using gross examination, histology, immunohistochemistry, and micro-computed tomography (μ-CT). Implanted BMMSCs were tracked using Adeno-LacZ labeling. The NELL-1-modified BMMSCs/PLGA group showed vigorous and rapid repair leading to regeneration of fibrocartilage at 6 weeks and to complete repair of native articular cartilage and subchondral bone at 24 weeks. The BMMSCs/PLGA group also completely repaired the defect with fibrocartilage at 24 weeks, but the cartilage in the BMMSCs/PLGA group was less well-organized than the NELL-1-modified BMMSCs/PLGA. The osteochondral defects in the PLGA and empty defect groups were poorly repaired, and no cartilage in the empty defect group or only small portion of cartilage in the PLGA group was found. In vivo viability of implanted cells was demonstrated by the retention for 6 weeks in the defects. These findings demonstrated that NELL-1-modified BMMSCs/PLGA composite can rapidly repair large osteochondral defect in the mandibular condyle with regeneration of native fibrocartilage and subchondral bone.

Repair of large osteochondral defects in rabbits using porous hydroxyapatite/collagen (HAp/Col) and fibroblast growth factor‐2 (FGF‐2)

Articular cartilage has a limited capacity for self-renewal. This article reports the development of a porous hydroxyapatite/collagen (HAp/Col) scaffold as a bone void filler and a vehicle for drug administration. The scaffold consists of HAp nanocrystals and type I atelocollagen. The purpose of this study was to investigate the efficacy of porous HAp/Col impregnated with FGF-2 to repair large osteochondral defects in a rabbit model. Ninety-six cylindrical osteochondral defects 5 mm in diameter and 5 mm in depth were created in the femoral trochlear groove of the right knee. Animals were assigned to one of four treatment groups: porous HAp/Col impregnated with 50 microl of FGF-2 at a concentration of 10 or 100 microg/ml (FGF10 or FGF100 group); porous HAp/Col with 50 microl of PBS (HAp/Col group); and no implantation (defect group). The defect areas were examined grossly and histologically. Subchondral bone regeneration was quantified 3, 6, 12, and 24 weeks after surgery. Abundant bone formation was observed in the HAp/Col implanted groups as compared to the defect group. The FGF10 group displayed not only the most abundant bone regeneration but also the most satisfactory cartilage regeneration, with cartilage presenting a hyaline-like appearance. These findings suggest that porous HAp/Col with FGF-2 augments the cartilage repair process.

Repair of experimentally induced large osteochondral defects in rabbit knee with various concentrations of Escherichia coli-derived recombinant human bone morphogenetic protein-2

Effective therapies for the regeneration of large osteochondral defects are still lacking; however, various approaches have been used. We evaluated the efficacy of Escherichia coli-derived dimeric recombinant human BMP-2 (E-rhBMP-2) for the repair of large osteochondral defects in a rabbit model. Osteochondral defects made in the femoral patellar groove of the knee were treated by transplanting gelatin sponges onto which no or various doses of E-rhBMP-2 were loaded. The outcomes were compared with those of an untreated control group four, 12 and 24 weeks after transplantation. At early time points, the cartilage tissue was repaired in a dose-dependent manner, and bone repair was accelerated in the defects treated with high doses of E-rhBMP-2. At 24 weeks, the repair of cartilage tissue was better with E-rhBMP-2 treatment, even at low doses, than without E-rhBMP-2 treatment. Our findings suggest that the use of E-rhBMP-2 improves and accelerates the repair of osteochondral defects in a rabbit model.

Evaluation of the activity of intraarticular hyaluronic acid in the repair of experimentally induced osteochondral defects of the stifle joint in dogs

The present study examined the results of using hyaluronic acid with autogenetic cancellous grafts in the treatment of experimentally induced osteochondral defects in the stifle joints of dogs. In this study, 10 mature dogs of different breeds, weights and of both sexes were used. General anesthesia and usual operation procedures were followed. A 10 mm deep defect was created on the femoral sulcus of the trochlea with a drill tip of 8 mm in diameter. The defects in the right and left legs were filled with autogenic cancellous grafts taken from the metaphysial region of the tibia. The left legs constituted the experimental group while the right legs served as control group. In the experimental group, 2 mg/kg intraarticular hyaluronic acid was twice administered into the stifle joint, i.e., immediately subsequent to the operation and 1 month afterwards. Parenteral antibiotics were prescribed postoperatively for ten days. Five animals were sacrificed at the third and sixth month after surgery. Macroscopic and microscopic findings obtained from each case were evaluated. On macroscopical examination, trochlear defects were determined to be incompletely filled at the third month in both control and experimental groups. On histopathologic examination, a loose fibrovascular formation in the area where the graft was applied was observed to be present in both control and experimental groups. However, in the experimental group this formation was more superficial, ossification activity was greater and trabeculous bone formation had been initiated. Macroscopical examination carried out in the sixth month determined that in the control group the defect surface did not fill up to the trochlear sulcus level. In the histopathologic examination, in control groups it was found that fibrocartilageous structures were developing in the fibrovascular space even though ossification was incomplete. The macroscopic examination showed that in the experimental group, the defect surface reached the trochlear sulcus level of defects in this month. The histopatologic examination revealed that fibrous tissue comprised a thin layer, under which ossification processes were complete and bone trabeculates fully formed. It was concluded that the usage of autogenic cancellous graft along with hyaluronic acid may be useful in the repair of large osteochondral defects.

Repair of large osteochondral defects with allogeneic cartilaginous aggregates formed from bone marrow‐derived cells using RWV bioreactor

Our objective was to examine the technique of regenerating cartilage tissue from bone marrow-derived cells by three-dimensional (3D) culture using the rotating wall vessel (RWV) bioreactor. Three-dimensional and cylindrical aggregates of allogeneic cartilage with dimensions of 10 x 5 mm (height x diameter) formed by the RWV bioreactor were transplanted into osteochondral defects of Japanese white rabbits (Group T, n = 15). For the control, some osteochondral defects were left empty (Group C, n = 18). At 4, 8, and 12 weeks postimplantation, the reparative tissues were evaluated macroscopically, histologically, and biochemically. In Group T at as early as 4 weeks, histological observation, especially via safranin-O staining, suggested that the reparative tissues resembled hyaline cartilage. And we observed no fibrous tissues between reparative tissue and adjacent normal tissues. In the deeper portion of the bony compartment, the osseous tissues were well remodeled. At 4 and 8 weeks postimplantation, the mean histological score of Group T was significantly better than that of Group C (p < 0.05). The glycosaminoglycans (GAG)/DNA ratio in both groups increased gradually from 4 to 8 weeks and then decreased from 8 to 12 weeks. We herein report the first successful regeneration of cartilage in osteochondral defects in vivo using allogeneic cartilaginous aggregates derived from bone marrow-derived cells by 3D culture using the RWV bioreactor.

Enhanced repair of large osteochondral defects using a combination of artificial cartilage and basic fibroblast growth factor

The purpose of this study was to examine the efficacy of a combination of artificial cartilage and basic fibroblast growth factor (bFGF) for the repair of large osteochondral defects. The artificial cartilage was a three-dimensional fabric (3-DF) composed of an ultra-high molecular weight polyethylene fiber with a triaxial three-dimensional structure. We implanted 3-DF impregnated with type I collagen gel containing 500 ng of bFGF (bFGF-treated group) or 3-DF impregnated with type I collagen gel alone (non-treated group) into a large full-thickness osteochondral defect (6×6×3 mm) of the patellar groove of rabbits. The defect area was examined grossly, histologically and biomechanically 4–48 weeks after surgery. Bone ingrowth into and around the 3-DF was evaluated with micro-computed tomography (μ-CT). Addition of bFGF to the 3-DF greatly accelerated cartilage formation on the articular surface and subchondral bone formation into and around the 3-DF, and improved biomechanical properties. These findings suggest that a combination of artificial cartilage and bFGF is clinically useful in cases involving large osteochondral defects.

Effects of basic fibroblast growth factor on the repair of large osteochondral defects of articular cartilage in rabbits: dose-response effects and long-term outcomes.

Articular cartilage possesses a limited capacity for self-renewal. The regenerated tissue often resembles fibrocartilage-like tissue rather than hyaline cartilage, and degeneration of the articular surface eventually occurs. The purpose of this study was to investigate the effect of basic fibroblast growth factor (bFGF) on the healing of full-thickness articular cartilage defects. bFGF (0, 10, 50, 100, 250, 500, or 1000 ng) was mixed with collagen gel and implanted into full-thickness articular cartilage defects drilled into rabbit knees. The repaired tissue was examined grossly and histologically, and was evaluated with the use of a grading scale at 4, 12, 24, and 50 weeks. At 4 weeks, treatment with 100 ng of bFGF had greatly stimulated cartilage repair both grossly and histologically in comparison with untreated defects (those filled with plain collagen gel). The average total scores on the histological grading scale were significantly better for the defects treated with bFGF than for the untreated defects. These improvements were evident as long as 50 weeks postoperatively, although slight deterioration was noted in the repaired cartilage. Immunohistochemical staining for type II collagen showed that this cartilage-specific collagen was diffusely distributed in the repaired tissue at 50 weeks. These findings suggest that bFGF may be a practical and important candidate for use in cartilage repair.

Tissue-engineered composites for the repair of large osteochondral defects.

To test the hypothesis that engineered cartilage can provide a mechanically functional template capable of undergoing orderly remodeling during the repair of large osteochondral defects in adult rabbits, as assessed by quantitative structural and functional methods. Engineered cartilage generated in vitro from chondrocytes cultured on a biodegradable scaffold was sutured to a subchondral support and the resulting composite press-fitted into a 7-mm long, 5-mm wide, 5-mm deep osteochondral defect in a rabbit knee joint. Defects left empty (group 1) or treated with cell-free composites (group 2) served as controls for defects treated with composites of engineered cartilage and the support, without or with adsorbed bone marrow (groups 3 and 4, respectively). Engineered cartilage withstood physiologic loading and remodeled over 6 months into osteochondral tissue with characteristic architectural features and physiologic Young's moduli. Composites integrated well with host bone in 90% of cases but did not integrate well with host cartilage. Structurally, 6-month repairs in groups 3 and 4 were superior to those in group 2 with respect to histologic score, cartilage thickness, and thickness uniformity, but were inferior to those in unoperated control tissue. At 6 months, Young's moduli in groups 2, 3, and 4 (0.68, 0.80, and 0.79 MPa, respectively) approached that in unoperated control tissue (0.84 MPa), whereas the corresponding modulus in group 1 (0.37 MPa) was significantly lower. Composites of tissue-engineered cartilage and a subchondral support promote the orderly remodeling of large osteochondral defects in adult rabbits.

Biological performance of a three-dimensional fabric as artificial cartilage in the repair of large osteochondral defects in rabbit.

A new artificial cartilage [A three-dimensional fabric (3-DF) comprising ultra-high molecular weight polyethylene fiber with a triaxial three-dimensional structure and coated with hydroxyapatite] was used to repair large osteochondral defects in rabbit knees. The knees with the 3-DF implanted in the osteochondral defects were evaluated 2-24 weeks after the operation macroscopically and microscopically. The 3-DF coated with hydroxyapatite was fixed firmly to the subchondral bone with the newly formed bone into and around the 3-DF. Hyaline-like cartilage was formed to a certain extent on the surface of the 3-DF, and the surface damage of the patella opposed to the 3-DF was minimal. In addition, the 3-DF caused no adverse effects such as particle disease, infection or severe synovitis during the experimental period. Consequently, the 3-DF seems to have successful biocompatibility in this rabbit experiment.

Cancellous bone grafting of large osteochondral defects: an experimental study in dogs

Autogenous cancellous bone was evaluated as a material to repair large osteochondral defects in 20 adult mongrel dogs. In one knee, the bone graft was used to fill an osteochondral cylindrical defect (10 mm diameter × 10 mm deep) created in the femoral trochlea. A similar lesion was created in the contralateral knee but was left untreated for spontaneous healing. Four animals were killed at each of five periods (2, 4, 8, 12, and 24 weeks), and the healing response of the defects was evaluated by gross anatomic inspection, plain film radiography, high-resolution radiography, and histology. The results of this study suggest that the use of a cancellous bone graft accelerates the repair of large osteochondral defects and produces more uniform filling of the defect than the ungrafted control. The reparative surface of the grafted lesions also differed from that of controls, having uniform coverage with histochemical-positive staining fibrocartilage at 8 weeks, a finding not observed in any control defect through the length of this study, 24 weeks. Arthroscopy 1998 Apr;14(3):311-20

Repair of large osteochondral defects: load-bearing and structural properties of osteochondral repair tissue

Morphology of osteochondral repair tissue determines its load-bearing capacity. Six millimetre diameter and 6 mm deep osteochondral defects were drilled in femoral condyles of goats and examined at 6 and 12 months. Morphology of normal cartilage and repair tissue was examined using scanning electron microscopy, picrosirius-polarisation microscopy and histology. Static contact pressures supported by normal cartilage and repair tissue were recorded using `Fuji Pressure Detection Film'. Normal morphology of articular cartilage was not restored. New tissue supported less pressure than the normal cartilage at 6 months. Contact pressure was further reduced after 12 months.

Abstract of Current Literature

Long‐Term Fate and Effects of Exercise on Sternal Cartilage Autografts Used for Repair of Large Osteochondral Defects in Horses by Howard RD, Mcllwraith CW, Trotter GW, Powers BE, McFadden PR, Harwood FL, Amiel D

Long-term fate and effects of exercise on sternal cartilage autografts used for repair of large osteochondral defects in horses

Summary Bilateral osteochondral defects (10 mm2 × 3 mm deep) were created on the distal articular surface of the radial carpal bone of ten, 2- to 3-year-old horses. One defect of each horse was repaired, using a sternal cartilage autograft (treated), and the other was left untreated (control). The horses were exercised on a high-speed treadmill at incrementally increased speed and duration over the course of 12 months. Horses were evaluated arthroscopically at 6 to 7 weeks, and clinical examinations were conducted weekly at exercise. Twelve months after surgery, carpuses of each horse were radiographed and clinically examined prior to euthanasia. A gross pathologic evaluation of each joint was conducted, and samples were collected for histologic, histochemical, histomorphometric, and biochemical evaluation. Radio-graphically, the grafted joints had more extensive evidence of arthropathy, and clinically, 8 of the 10 horses were more lame in the grafted limb. On the basis of histomorphometry, the repair tissue of the grafted defects contained a greater median percentage of hyaline cartilage (45%) than that of control defects (4.5%), and the control defects contained a greater percentage of fibrocartilage (82%) than did grafted defects (28.5%). A greater median percentage of repair tissue stained with safranin-O in the grafted defects (24.5%) than in the control defects (3.5%). On gross pathologic and histologic evaluation, repair tissue of the control defects had better continuity and was more firmly attached to the subchondral bone than was repair tissue of the grafted defects. Repair tissue of the grafted defects had extensive fissure and flap formation. Histologically, subchondral bone reactivity and fibroplasia was extensive in grafted joints. Repair tissue of grafted defects had a greater percentage of type II collagen (mean ± SEM, 83.5 ± 2.95%) than did controls (mean, 79.4 ± 3.87%) that was not statistically significant. Hexosamine content was significantly higher (P &lt; 0.05) in repair tissue of the grafted defect (mean, 28.9 ± 3.00 mg/g of dry weight) vs control (mean, 20.6 ± 1.85 mg/g of dry weight). On the basis of this experimental model, sternal cartilage autografts cannot be recommended at this time for repair of osteochondral defects in athletic horses.

Experimental Studies on Repair of Large Osteochondral Defects at a High Weight Bearing Area of the Knee Joint: A Tissue Engineering Study

There is a vast clinical need for the development of an animal model to study the fundamentals of healing of injured or diseased diarthrodial joints (knee, hip, shoulder, wrist, etc). Current prosthetic replacements do not offer acceptable treatment for injuries and diseases of these joints in young active individuals. New clinical treatment modalities, based on sound biologic principles, are sought for the development of repair or healing tissues engineered to have similar biomechanical properties as normal articular cartilage. In this paper we present a brief review of this need, and propose a grafting procedure which may lead to a successful animal model for studies of long term repair of major osteochondral defects. This grafting procedure uses an autologous periosteum-bone graft or an autologous-synthetic bone replacement graft. We have applied these grafts for in vivo repair of large surgically created defects in the high weight bearing area of the distal femoral condyle of mature New Zealand white rabbits. Further, an interdisciplinary study, including histochemistry, biochemistry (composition and metabolic activities), and biomechanics (biphasic properties), was performed to assess the feasibility of our animal model to generate viable repair tissues. We found our grafting procedure produced, 8 weeks postoperatively, tissues which were very similar to those found in normal articular cartilage. However, our histological studies indicate incomplete bonding between the repair tissue and the adjacent cartilage, and lack of an appropriate superficial zone at the articular surface. These deficiencies may cause long term failure of the repair tissue. Further studies must be undertaken to enhance development of a strong bond and a collagen-rich surface zone. This may require the use of growth factors (e.g., transforming growth factors beta) capable of simulating extra collagen production, or the use of serum derived tissue glue for bonding. At present, we are pursuing these studies.